It is proposed to study inhibition of ATP-driven reverse electron flow catalyzed by bovine heart submitochondrial particles to gain further insight into the nature of inhibition of this reaction by ADP. Inhibition by other substrate or product analogs will be studied to attempt to clarify more precisely the mechanism of the reaction and the involvement of ADP and Pi as feed-back inhibitors. Oxygen-18 studies will be continued in an attempt to delineate the nature of the characteristic uncoupler-resistant Pi yields reversibly H2O exchange which accompanies ATP hydrolysis sustained by an ATP-regenerating system. It is hoped that these studies will provide new insights into some key energy-related mitochondrial processes and may also seve to provide information about potential regulatory processes in ischemic heart tissue. BIBLIOGRAPHIC REFERENCES: The effects of ADP on reverse electron flow and the oxygen exchange reactions catalyzed by bovine heart muscle sub-mitochondrial particles. R.A. Mitchell, J.A. Russo, and C.M. Lamos (1975). J. Supramol. Struc. (in press). Kinetic evidence for an extracatalytic regulatory site on sub-mitochondrial particles which is accessible to ADP but not to ethenoadenosine nucleotides. R.A. Mitchell, J.A. Russo, C.M. Lamos (1975). Fed. Proc., abstract.